tbuckley/cabot-search huggingface dataset:
Abstract P308: The Determinants of Fasting and Post-Load Non-Esterified Fatty Acids in Older Adults: The Cardiovascular Health Study
Authors: Yakubu Bene-Alhasan, David S Siscovick, Joachim H Ix, Jorge R Kizer, Russell Tracy, Luc Djousse, Ken J Mukamal
Journal: Circulation (2023)

Aim: Non-esterified fatty acids (NEFA) are associated with key cardiometabolic diseases of aging and are potential targets for prevention, but their population-level correlates remain uncertain. We sought to identify modifiable factors associated with higher fasting and post-load NEFA levels in older adults. Methods: We used linear multivariable regression models to determine the cross-sectional associations of demographic, anthropometric, lifestyle characteristics, and medication use with serum fasting and post-load NEFA concentrations amongst community-dwelling older adults enrolled in the Cardiovascular Health Study (n = 1,924). Results: In general, fasting NEFA levels demonstrated a broader set of determinants, while post-load NEFA were more consistently associated with metabolic factors. Waist circumference and weight were associated with higher fasting and post-load NEFA. Cigarette smoking and caffeine intake were associated with lower levels of both species, and moderate alcohol intake was associated with higher fasting levels whereas greater consumption was associated with lower post-load levels. Unique factors associated with higher fasting NEFA included female sex, higher age, loop and thiazide diuretic use and calcium intake, while factors associated with lower fasting levels included higher educational attainment, beta-blocker use, and protein intake. Hours spent sleeping during the daytime were associated with higher post-load NEFA, while DASH score were associated with lower levels. Conclusion: Fasting and post-load NEFA appear to have both common and unique modifiable risk factors, including sociodemographics, anthropometric, medications, and diet. Post-load NEFA were particularly sensitive to metabolic factors, while a broader range of determinants were associated with fasting levels. These factors warrant further study as targets for lowering levels of NEFA in older adults..
Abstract P612: Alcohol Intake, Kidney Function and Mortality
Authors: martino laurenzi
Journal: Circulation (2023)

Background: Data from the Gubbio population study were used to investigate the association of alcohol intake, kidney function and mortality. Methods: The Gubbio Study is a longitudinal study on the population of Gubbio, a town in central Italy; it started in 1983, addressing the resident population aged 5 +. Three exams were performed: Exam 1 (baseline) Exam 2 (6-year follow-up) and Exam 3 (20-year follow-up); this analysis is on the 2,069 adult participants (42.8% male) with complete data at Exam 3. Kidney function was estimated as glomerular filtration rate (eGFR) with the CKD-Epi equation, mL/min x 1.73 m 2 . Habitual alcohol intake was assessed by standard questionnaires. Mortality was derived from official records. Results: Wine intake accounted for &gt;94% of total alcohol intake at all exams. Alcohol intake tracked significantly over time (R &gt; 0.66, P &lt; 0.001). Daily alcohol intake distribution was skewed at all exams (skewness &gt; 2); we divided it into four strata (grams/day = 0, 1-24, 25-48, and &gt; 48). The goodness of the fit of the strata was confirmed by lab markers of alcohol intake (P&lt;0.001). In multi-variable regression, strata related cross-sectionally to eGFR at all exams and were correlated longitudinally with less negative eGFR change from Exam 1 to Exam 2 and from Exam 2 to Exam 3. In multi-variable Cox models, compared to no intake, intakes &gt; 24 g/d were not correlated with a different mortality while an intake of 1-24 g/d was correlated with a lower mortality in the whole cohort (HR= 0.77, P=0.003) and in the subgroup with eGFR &lt; 60 mL/min x 1.73 m 2 (HR= 0.69, P=0.033). Conclusion: These data indicate a positive independent association of moderate daily alcohol intake with kidney function not due to a mortality-related selection.
Abstract MP66: The Interplay Between Diet, Circulating Indolepropionate Concentrations, and Cardiometabolic Health in US Populations
Authors: Yang Hu, Jun Li, Lu Zhu, Biqi Wang, Yanping Li, Kerry L Ivey, Kyu Ha Lee, A.Heather Eliassen, Qibin Qi, Andrew Chan, Curtis Huttenhower, Eric B Rimm, Frank B Hu, Qi Sun
Journal: Circulation (2023)

Background: Indolepropionate (IPA), a tryptophan metabolite of human gut microbiota origin, is associated with lower risk of type 2 diabetes (T2D) in humans. The complex interplay among tryptophan intake, the gut microbiome, prebiotics, circulating IPA concentrations, and T2D risk has not been investigated. Objectives: We aimed to identify IPA-producing gut microbiota species and investigate potential diet-microbiota interaction on circulating IPA concentrations. Methods: We included 287 men from the Men’s Lifestyle Validation Study, a sub-study of the Health Professionals Follow-Up Study (HPFS), who provided up to two pairs of fecal samples and two blood samples approximately six months apart. Dietary intake was assessed using 7-day diet records. We identified microbial taxonomic features associated with plasma IPA concentrations using generalized linear regression and calculated a rank-based species score to reflect IPA-producing potential. Associations between plasma concentrations of tryptophan metabolites and T2D risk were examined in 13,032 participants from Nurses’ Health Study (NHS), NHSII, and HPFS. Results: Plasma IPA concentrations were associated with overall gut microbial profiles (permutational analysis of variance test, p=0.001). We identified 17 microbial species, such as Eubacterium eligens, Butyrivibrio crossotus , and Faecalibacterium prausnitzii , whose abundance was significantly associated with increased plasma IPA concentrations (false discovery rate &lt; 0.05). A significant association between higher tryptophan intake and higher IPA concentrations was only observed among men who had higher fiber intake and a higher microbial species score consisting of the 17 species (p-interaction &lt; 0.01). Similar modulation was also observed for major tryptophan food contributors including vegetables (p-interaction &lt; 0.01), red/processed meat (p-interaction = 0.02), egg (p-interaction 0.01), dairy (p-interaction = 0.01), and whole grain (p-interaction &lt; 0.01). Moreover, interactions persisted for all fiber subtypes (soluble/insoluble fiber and pectin). We documented 1,744 incident T2D cases during 218,603 person-years of follow-up. Plasma concentrations of tryptophan and three kynurenine-pathway metabolites (kynurenine, xanthurenate, and quinolinate) were positively associated with T2D risk while an inverse association was found for IPA. Conclusions: Specific microbial species and dietary fiber jointly modulate the associations between tryptophan intake and circulating IPA concentrations. In a subsequent analysis, IPA levels were predictive of lower T2D risk. Our findings suggest that the health effects of dietary tryptophan may depend on both gut microbiome composition and prebiotic consumption.
Abstract MP33: Increases in the Ratio of Waist Circumference-Decile to Body Mass Index-Decile With Age: Findings From the National Health and Nutrition Examination Survey
Authors: Orna Reges, Tsafnat Test, Ira Gaidishev, Limor Beshari, Shiraz Aharoni, Rinat Greenberg, Maxim Melichov, Dror Dicker, Tomas Karpati
Journal: Circulation (2023)

Introduction: The predictive capability of waist circumference (WC) and body mass index (BMI) in cardiometabolic risk is well known. Both indices increase with age, yet the changes in WC relative to BMI, especially for a given BMI category, are not fully understand. This study aimed to assess changes with increasing age, of the ratio of WC-decile to BMI-decile (WC-d/BMI-d), stratified by sex and BMI categories. Hypothesis: WC-d/BMI-d increases with age, with significant differences within sex and BMI categories. Methods: For 29,256 participants (mean age: 47.8 years, 51% women) of the National Health and Nutrition Examination Survey during 2008-2017, WC-d and BMI-d (range 1-10 for both) were defined, and WC-d/BMI-d was calculated. Multivariable linear regression was used to assess the independent association of age with WC-d/BMI-d. The model was adjusted for sex, ethnicity, and comorbidities. The interaction terms age x sex and age x BMI category were incorporated into the model. Separate models were applied for males, females, and BMI categories. Results: In multivariable linear regression, WC-d/BMI-d increased with age among the total study population (0.006, p&lt;0.001); and the interaction terms age x sex and age x BMI-category were significant (p&lt;0.001for both). The increasing trend of WC-d/BMI-d with age was significant for males (0.008, p&lt;0.001), females (0.004, p&lt;0.001), and the BMI groups examined (normgal weight: 0.011, p&lt;0.001, overweight: 0.007, p&lt;0.001, and obesity: 0.002, p&lt;0.001). Greater increases were found among males (Figure 1A) and among individuals with normal BMI level (Figure 1B). Conclusion: The increase in WC-d/BMI-d with age reflects a steeper increase in WC than in BMI, with greater changes among males and among individuals with normal BMI level. These results emphasize the importance of WC measurement in clinical practice, especially among males and individuals with normal BMI. It is worth considering WC-d/BMI-d as an additional measure in obesity management among adults.
Abstract P670: Association of Left Atrial and Left Ventricular Sphericity With Left Ventricular Structure and Function
Authors: Viktoria Mladenovik, Zhiyong Dong, Ngo Long, Ewa Osypiuk, birgitta lehman, David D McManus, Emelia J Benjamin, Gary F Mitchell, Vasan S Ramachandran, Susan Cheng, Connie W Tsao
Journal: Circulation (2023)

Introduction: Spherical remodeling of atria and ventricles is associated with cardiovascular disease (CVD) and mortality. We hypothesized that volumetric left atrial (LA) and left ventricular (LV) sphericity index (SI) are associated with adverse measures of LV structure and function in older adults free of CVD. Methods: Framingham Heart Study 2nd generation participants without prevalent CVD with echocardiography at exam 8 were studied (n=1701). Volumetric LA SI was calculated as the ratio of biplane LA volume to the volume of a sphere [4/3*pi*(r^3)] calculated using the radius of LA length (r=½ average length of the atria in 4- and 2-chamber views in diastole). Volumetric LV SI was calculated as the ratio of LV end-diastolic volume (LVEDV) to the volume of a sphere calculated using the radius of LV length (r= ½ length of LV in 4-chamber view in diastole). LVEDV was measured by biplane area-length method. In multivariable models adjusting for CV risk factors including age, sex, BMI, hypertension, dyslipidemia, diabetes, and smoking, we evaluated the relations of LA and LV SI with echocardiographic LV structure and function: wall thickness (septal and posterior wall average), mass, global longitudinal strain, ejection fraction (EF), and log-transformed mitral Doppler E/A. β coefficients are presented as standard deviation (SD) change in outcome per SD change in predictor variable. Results: Descriptives are presented in the Table . There was no association of LA or LV SI with sex (p=0.48, p=0.61, respectively). LA SI was associated with worse (positive) LV global longitudinal strain (std β±SE: 0.08±0.03, p=0.016). LV SI was associated with LV wall thickness (std β±SE: 0.24±0.03, p&lt;0.0001), mass (0.45±0.03, p&lt;0.0001) and log-Doppler E/A (0.07±0.03, p=0.015) and was inversely associated with LV EF (-0.12±0.03, p&lt;0.0001). Conclusions: In a large community sample without prevalent CVD, spherical remodeling of the heart was associated with unfavorable LV structure and both systolic and diastolic dysfunction.
Abstract MP36: Long-Term Dietary Lignan Intake and Weight Change: Results From Three Prospective Cohort Studies
Authors: Sharan K Rai, Yang Hu, Ming Ding, Frank B Hu, Molin Wang, Jorge E Chavarro, Qi Sun
Journal: Circulation (2023)

Objectives: Studies suggest that endogenous estrogen may be involved in regulating body weight. Dietary lignans can act as estrogen receptor agonists and may be beneficial for weight control. We prospectively examined the association between changes in dietary lignan intake with weight change. Methods: We analyzed data from 124,875 men and women in the Nurses’ Health Study (1986-2010), Nurses’ Health Study II (1991-2011), and the Health Professionals Follow-up Study (1986-2010). We calculated 4-year changes in total lignan intake as well as in four major individual lignans (matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol) using data from a semi-quantitative food frequency questionnaire. Participants reported their height and weight at baseline and updated their current weight every 2 years thereafter, from which we calculated 4-year changes in weight as the primary study outcome. We used multivariable generalized linear regression models to examine the association between 4-year changes in lignan intake with 4-year weight changes over the same period, and these models were adjusted for age, baseline BMI in each period, and relevant lifestyle factors. Results: Each 1-standard deviation (SD) increase in total lignan intake was associated with a 4-year weight change of -0.36 lbs (95% confidence interval [CI] -0.40 to -0.33 lbs; P for trend &lt;0.0001). This inverse association persisted among all four individual lignans, although the magnitude of this association was the strongest for lariciresinol (-0.63 lbs [95% CI, -0.67 to -0.59 lbs]; P for trend &lt;0.0001) (Figure) . The observed associations were stronger among certain subgroups, including those with BMI ≥25 kg/m 2 , below-median diet quality, or below-median physical activity level. Conclusions: Increases in dietary lignan intake were associated with less weight gain over the same 4-year period. Our findings support existing dietary recommendations to consume a healthy plant-based diet.
Abstract MP29: High-Sensitivity Troponin-T is Associated With Incident Diabetic Foot Infections in the Atherosclerosis Risk in Communities Study
Authors: Caitlin W Hicks, Dan Wang, Katherine McDermott, Michael Fang, Kunihiro Matsushita, B Gwen Windham, Elizabeth Selvin
Journal: Circulation (2023)

Background: Diabetic foot infections (DFI) are associated with substantial morbidity and mortality. Glycemic control and prevalent cardiovascular disease have been associated with DFI risk, but the association of subclinical cardiovascular disease with incident DFI has not been explored. Hypothesis: We hypothesized that high-sensitivity troponin-T (hs-cTnT, a marker of microvascular disease) and N-terminal-pro hormone BNP (NT-proBNP, a marker of cardiac wall stress) would be associated with incident DFI in adults without prevalent cardiovascular disease. Methods: We conducted a prospective cohort analysis of 1733 Black and White participants in the Atherosclerosis Risk in Communities (ARIC) study who had diabetes without prevalent cardiovascular disease at visit 2 (1990-1992, mean age 57.7 yrs). We estimated the cumulative incidence of incident DFI through 2019 using hospitalization discharge codes. We used Cox models to assess the associations of categories of cardiac biomarkers (using clinical cut-points) with DFI after adjusting for traditional risk factors. Results: During a median follow-up of 25 years, there were 417 incident DFI events. The 25-year cumulative incidence of DFI was higher among participants with elevated hs-cTnT (≥14 ng/L) vs not elevated (35% vs. 21%; P&lt;0.001), but not among participants with elevated NT-proBNP (≥125 pg/mL) (23% vs. 23%; P=0.73). In adjusted models, elevated hs-cTnT was associated with incident DFI (HR 1.98, 95%CI 1.46, 2.68). Elevated NT-proBNP was not significantly associated with incident DFI (HR 1.04, 95%CI 0.78, 1.41). Our results were similar when the biomarkers were modeled more flexibly using splines: we observed a robust association of hs-cTnT, but not NT-proBNP, with incident DFI ( Figure ). Conclusions: Elevated hs-cTnT was associated with incident DFI among middle-aged adults without prevalent cardiovascular disease. This suggests subclinical cardiovascular disease, possibly in the form of microvascular ischemia, may play a role in the etiology of DFI.
Abstract MP37: DNA Methylation of Leptin Mediates the Relationship Between Stress-Associated Inflammation and Insulin Resistance: Data From the Washington DC Cardiovascular Health and Needs Assessment
Authors: Lola R Ortiz-Whittingham, Yvonne Baumer, Billy S Collins, Valerie M Mitchell, Michael J Corley, Tiffany M Powell-Wiley
Journal: Circulation (2023)

Introduction: Chronic psychosocial stressors are associated with inflammation and cardiovascular (CV) risk, including insulin resistance (IR); however, potential DNA methylation (DNAm) mediators between stress-related inflammation and IR are not known. Hypothesis: DNAm biomarkers mediate the relationship between stress-related inflammation and IR. Methods: Participants from the DC Cardiovascular Health and Needs Assessment (DC-CHNA) underwent phenotyping at the NIH Clinical Center. Homeostatic Model Assessment for Insulin Resistance was calculated using insulin and glucose values. Social isolation, loneliness, and depression were determined using validated surveys. IL-8 was measured using an ELISA-based method. Principal component DNAm-based surrogate markers of leptin, cystatin C, and plasminogen activator inhibitor-1 were calculated from DNAm data obtained from participants' buffy coat samples. We examined relationships of interest with regression models adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score and body mass index (BMI). Mediation analysis was used to evaluate DNAm measures as possible mediators. Results: The DC-CHNA consisted of 60 African American participants (mean age 61±11 years, 93% female) with ASCVD risk. Social isolation (β=0.34, p=0.009) and depression (β=0.30, p=0.04) associated with IL-8. IL-8 then inversely associated with DNAm-based surrogate leptin levels and directly associated with IR; leptin DNAm mediated the IL-8-IR relationship ( Figure ). Conclusions: We show a relationship between stress-associated IL-8 and IR mediated by DNAm-based surrogate leptin levels. While relationships between inflammation, serum leptin, and IR are documented, the impact of chronic stress on leptin DNAm in the context of CV risk requires further investigation in larger, diverse cohorts. DNAm-based surrogate markers of plasma proteins, such as leptin, could serve as a marker for increased CV risk in populations disproportionately exposed to chronic stress.
Abstract P426: Food Insecurity is Associated With Insomnia Among Men in the Echorn Cohort
Authors: Carol R Oladele, Johanna E Elumn, Deron Galusha, Neha Khandpur, Josefa L Martinez-Brockman, Marcella Nunez-Smith
Journal: Circulation (2023)

Background: Food insecurity (FI), defined as lack of consistent access to enough food for an active, healthy lifestyle, affects 40% of people across the Caribbean and is associated with adverse cardiovascular outcomes. Despite evidence that suggests an association between FI and sleep health and FI prevalence in the Caribbean, few studies have been conducted. We aimed to examine the relationship between FI and sleep health in the Eastern Caribbean.We hypothesized that FI would be negatively associated with sleep health. Methods: Baseline data from the Eastern Caribbean Health Outcomes Research Network Cohort Study (ECS) were analyzed (2013-2018). Participants (n= 2,961) are community-dwelling individuals 40 years or older residing in Barbados, Puerto Rico, Trinidad and Tobago, or U.S. Virgin Islands. Participants completed a questionnaire including the 9-item Latin American and Caribbean Food Security Scale. Responses were summed to create a score (0-9) and create four categories: 0 no FI, 1-3 mild FI, 4-6 moderate, and 7-9 severe FI. FI was also operationalized as a binary variable (yes/no). Sleep outcomes included adequate sleep and insomnia. Sleep variables were measured by the items, “how many hours of sleep do you usually get at night,” and “has a doctor or other health professional has ever told you that you have insomnia.” Adequate sleep was defined as 7+ hours (yes/no) and insomnia was also operationalized as binary variable (yes/no). Other variables included sex and age. Chi-square tests and multivariable logistic regression modeling were used for the analysis. Results: Analyses included 2,321 participants. Sixty-five percent were women, and the mean age was 57 years. Findings showed 28% (644 of 2,321) of participants experienced food insecurity: 17.1% (397 of 2,321) mild, 6.2% (144 of 2,321) moderate, and 4.4% (103 of 2,321) severe. Fifty-five percent (1279 of 2,321) of participants had inadequate sleep (&lt;7 hours) and five percent reported insomnia. FI was not significantly associated with inadequate sleep in bivariate or multivariable analyses. Bivariate results for insomnia showed statistically significant associations with FI (p=0.0002). Multivariable results showed moderate and severe FI were associated with 2 (CI=1.01-4.16) and 4 (CI=1.95-7.05) times greater odds of insomnia compared to those who were food secure. Sex-stratified results showed men with severe FI had 9 times greater odds of insomnia (CI=3.2-23.7). Results were not statistically significant for women. Conclusions: Future research should examine mechanisms that explain sex differences in the relationship between FI and insomnia.